| dc.description.abstract | The condensation of DNA, a process where DNA molecules are tightly packed together, plays a crucial role in various biological processes, as well as the first step in the delivery of DNA to cells in gene delivery. One promising approach of the latter involves using poly(amidoamine) (PAMAM) dendrimers to induce the condensation of DNA molecules. Still, the toxicity of PAMAM dendrimers is often correlated with their molecular weight and generation.
To enhance DNA condensation and transfection efficiency while minimizing toxicity, I explored the condensation of DNA molecules using peptide-conjugated dendrimers as condensing agents and conjugated peptides to lower generations of PAMAM dendrimers.
The effect of the overall charge of the condensed DNA was investigated using positively charged PAMAM dendrimers G4 and G2 which bind to the plasmid DNA (Gwiz-Luc). Peptides with varying amino acid composition were used to study their effect on DNA condensation.
Atomic Force Microscopy (AFM) was employed to visualize the condensation process and characterize the resulting structures at the nanoscale and the interactions of DNA with PAMAM dendrimer G2, and G4 and peptide conjugated G2, were studied using AFM. The images are of 512×512 pixels using tapping in air mode.
At charge ratios 1.0 and 2.0, the complexes of DNA and PAMAM were observed, and at a charge ratio of 2.0, DNA adopts more condensed structures. For peptide conjugated G2, the condensation of DNA increased as compared to condensation by the nonconjugated dendrimers.
In this thesis, the impact of conjugating peptides to G2 PAMAM dendrimers on DNA condensation has been investigated and shows a variety of morphologies such as rod-like or hairpin, in addition to semi-spherical shapes are formed.
The resulting condensed structures exhibited well-defined morphologies, suggesting the potential utility of these dendrimers in DNA nanotechnology and gene delivery applications. This study provides valuable insights into the mechanisms of DNA condensation and highlights the role of peptide-conjugated dendrimers as promising candidates for biotechnological and therapeutic advancements.
Keywords: DNA condensation, peptide-conjugated dendrimers, atomic force microscopy, nanobiotechnology, gene delivery. | |
